Synergistic Antimicrobial Preparations Containing Chlorite and Hydrogen Peroxide

ABSTRACT

Antimicrobial/pharmaceutical preparations (e.g., solutions, gels, ointments, creams, sustained release preparations, etc.) which comprise chlorite (e.g., a metal salt of a chlorite) in combination with a peroxy compound (e.g., hydrogen peroxide), and methods for using such preparations for disinfection of articles or surfaces (e.g., contact lenses, counter tops, etc.), antisepsis of skin or other body parts, prevention or deterrence of scar formation and/or treatment and prophylaxis of dermal (i.e., skin or mucous membrane) disorders (e.g., wounds, burns, infections, cold sores, ulcerations, psoriasis, acne, or other scar-forming lesions).

RELATED APPLICATIONS

This is a continuation of copending U.S. patent application Ser. No.10/938,797 filed Sep. 9, 2004, which is a continuation of U.S. patentapplication Ser. No. 10/308,229 filed Dec. 2, 2002, which is acontinuation of U.S. patent application Ser. No. 09/722,919 filed Nov.27, 2000 and issued as U.S. Pat. No. 6,488,965, which is a continuationof U.S. patent application Ser. No. 09/169,620 filed Oct. 8, 1998, theentire disclosure of each such patent and application being expresslyincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to medical compositions andmethods, and more particularly to certain disinfectant/antimicrobialpreparations and methods for using such preparations i) to disinfectarticles or surfaces, ii) as a topical antiseptic for application tobody parts, and iii) to prevent or deter scar formation and iv) to treatdermatological disorders such as wounds, burns, ulcers, psoriasis, acneand other scar forming lesions.

BACKGROUND OF THE INVENTION A. Antimicrobial and Disinfectant/AntisepticAgents Used for Disinfection/Antisepsis and Topical Treatment of Wounds,Burns, Abrasions and Infections

The prior art has included numerous antimicrobial agents which havepurportedly been useable for disinfection of various articles and/or fortopical application to a living being for antisepsis and/or treatment ofdermal disorders (e.g., wounds, burns, abrasions, infections) wherein itis desirable to prevent or deter microbial growth to aid in healing.Such topical antimicrobial agents have contained a variety of activemicrobicidal ingredients such as iodine, mercurochrome, hydrogenperoxide, and chlorine dioxide.

i. Prior Chlorine Dioxide Preparations

Chlorite, a precursor of chlorine dioxide, is known to be useable as adisinfectant for drinking water and as a preservative for contact lenscare solutions. However, chlorite exhibits only weak microbicidalactivity within a concentration range that is acceptable and safe fortopical application to the skin (e.g., 200-1000 parts per million).Thus, chlorite has not been routinely used as an active microbicidalingredient in preparations for topical application to the skin.

In view of the limited usefulness of chlorite as an antiseptic ortopical microbicide, various compositions and methods have been proposedfor activation or enhancement of the microbicidal activity of chlorite.Examples of such compositions and methods for activation or enhancementof the microbicidal activity of chlorite are described in U.S. Pat. No.4,997.616 (describing general activation); U.S. Pat. No. 5,279,673(describing acid activation) and U.S. Pat. No. 5,246,662 (describingtransitional metal activation).

Chlorine dioxide (CO₂) and “stabilized chlorine dioxide” are known to beuseable as antiseptics. Chemically, chlorine dioxide is an oxidizingagent which has strong microbicidal activity. Chlorine dioxide isgenerally regarded as superior even to gaseous chlorine, in certainwater treatment applications where it is used as to eliminate algae andother organic material and/or to remove odors or tastes. Chlorinedioxide is also effective as a microbicide, for elimination of bacteria,viruses, and microbial spores.

In addition to its use as a microbicide, chlorine dioxide is a highlyreactive, unstable radical which is useable as an oxidizing agent in anumber of other chemical and biochemical applications. For example, asdescribed in U.S. Pat. No. 4,855,135, chlorine dioxide can be used for(a) oxidation of double bonds between two carbon atoms; (b) oxidation ofunsaturated fatty acids (lipids) via double bonds between two carbonatoms; (c) acceleration of hydrolysis of carboxylic anhydrides; (d)oxidation of aldehydes to the corresponding carboxylic acids; (e)oxidation of alcohols; (f) oxidation of amines; (g) oxidation ofphenols, phenolic derivatives and thiophenolic compounds; (h) moderateoxidation of hydroquinones; (i) oxidation of amino acids, proteins andpolyamides; j) oxidation of nitrates and sulphides; and (k) alterationof the CHO and CH₂OH radicals of carbohydrates to produce carboxylicfunctionality.

Concentrated chlorine dioxide in its liquid or gaseous state is highlyexplosive and poisonous. As a result, concentrated chlorine dioxide mustbe handled and transported with great caution. For this reason, it isgenerally not feasible to dispense pure chlorine dioxide for use as atopical antimicrobial agent or disinfectant. Instead, same antimicrobialor disinfectant preparations have been formulated to provide for “acidgeneration” of chlorine dioxide. Such acid generation solutions containa metal chlorite (i.e., a precursor of chlorine dioxide available inpowdered or liquid form) in combination with an acid which will reactwith the chlorite to liberate or release chlorine dioxide. Generally,any acid may be used for acid generation of chlorine dioxide, includingstrong acids such as hydrochloric acid and sulfuric acid and relativelyweak acids such as citric and tartaric acid. Drawbacks or problemsassociated with these prior chlorine dioxide generating systems includea) the inconvenience of handing two separate containers or chemicalcomponents, b) the difficulty of delivering such two-component systemsto the intended site of application, and c) the fact that these priorsystems are of acid, rather than neutral, pH. Moreover, the priorchlorine dioxide generating systems which utilize acid-inducedgeneration of chlorine dioxide can, if uncontrolled, cause thegeneration of chlorine dioxide to occur quite rapidly and, as a result,the disinfectant or antimicrobial potency of the solution may be shortlived. Increasing the concentration of chlorite and acid within thesolution may prolong its disinfectant or antimicrobial shelf life, butsuch Increased concentrations of these chemicals can result intoxicities or (in topical applications) skin irritation. Such increasedconcentrations may also result in the generation of more chlorinedioxide than is required.

Various methods have been described to limit or control the rate atwhich chlorine dioxide is produced in “acid generation” solutions. Forinstance, U.S. Pat. No. Re. 31,779 (Alliger) describes a germicidalcomposition which comprises a water soluble chlorite, such as sodiumchlorite, in combination with lactic acid. The particular compositionpossesses improved disinfectant properties, properties not attained byusing the same composition but replacing the lactic acid with otheracids such as phosphoric acid, acetic acid, sorbic acid, fumaric acid,sulfamic acid, succinic acid, boric acid, tannic acid, and citric acid.The germkilling composition is produced by contacting an acid materialcontaining at least 15% by weight of lactic acid with sodium chlorite inaqueous media, the amount of lactic acid being sufficient to lower thepH of the aqueous media to less than about 7. The methods disclosed ofdisinfecting and sanitizing a germ-carrying substrate, such as skin,include either application of the germ-killing composition, orapplication of the reactants to provide in situ production thereof.Also, U.S. Pat. No. 5,384,134 (Kross) describes acid induced generationof chlorine dioxide from a metal chlorite wherein the chloriteconcentration is limited by the amount of available chlorous acid. Inparticular, the Kross patent describes a method for treating dermaldisorders wherein a first gel, which comprises a metal chlorite, ismixed with a second gel, which comprises a protic acid. The chloriteions present in such solution as chlorous acid purportedly comprise nomore than about 15% by weight of the total chlorite ion concentration inthe composition, and the mixture of the two gels purportedly generateschlorine dioxide over an extended time of up to 24 hours.

Other prior patents have purported to describe the use of “stabilized”chlorine dioxide as a means of chlorine dioxide generation. The termstabilized chlorine dioxide refers to various compositions in which thechlorine dioxide is believed to be held in solution in the form of alabile complex. The stabilization of chlorine dioxide by the use ofperborates was disclosed in U.S. Pat. No. 2,701,781 (de Guevara).According to the de Guevara patent, an antiseptic solution of stabilizedchlorine dioxide can be formed from an aqueous solution of chlorinedioxide and an inorganic boron compound with the boron compound and thechlorine dioxide being present in the solution as a labile complex. Thechlorine dioxide, fixed in this stable condition, is an essentialingredient of the antiseptic solution. The de Guevara patent disclosesthat the chlorine dioxide may be introduced into the compositions eitherby in situ generation or it may be generated externally and introducedinto the solution, as by bubbling the chlorine dioxide gas into theaqueous solution. Various methods may be employed for the externalproduction of the chlorine dioxide, such as reaction of sulfuric acidwith potassium chlorate or the reaction of the chlorate with moistoxalic acid. Alternatively, chlorine dioxide can be generated in situ byreaction of potassium chlorate and sulfuric acid. Note that whether thechlorine dioxide is produced in situ or externally, it is essentially anacid induced liberation of the chlorine dioxide from potassium chlorate.

U.S. Pat. No. 4,317,814 (Lasa) describes stabilized chlorine dioxidepreparations for treatment of burns in humans. Aqueous mixtures ofperborate stabilized solutions of chlorine oxides, such as chlorinedioxide, in combination with glycerin are described for topicalapplication to burned areas and may also be administered by oralapplication for treatment of bums. The aqueous solutions of perboratestabilized chlorine oxides are disclosed as being prepared by mixingwith water the following: sodium chlorite, sodium hypochlorite,hydrochloric acid, sulfuric acid, an inorganic perborate, and a peroxycompound, such as sodium perborate. Thus, the solutions prepared inaccordance with the Laso patent contain chlorine dioxide, hypochloriteand peroxy compounds as strong oxidizing agents and appear to utilizeacid activation of the chlorine dioxide. The Laso patent states that themethods disclosed therein resulted in an immediate subsidence of burnrelated pain in many cases, that healing was rapid and characterized byan absence of infection or contraction, and that the burn scars weresmooth and resembled normal tissue, thus eliminating the need forplastic surgery in certain cases. However, long term storage andstability are issues with the aqueous solutions described in theabove-identified Laso patent, because such mixtures tend to generatechlorine dioxide very quickly, thus diminishing the long term stabilityof such mixtures.

U.S. Pat. No. 3,271,242 (McNicholas et al.) describes stabilizedchlorine dioxide solutions which are formed by combining chlorinedioxide gas with an aqueous solution containing a peroxy compound, andsubsequently heating the solution to a temperature which is high enoughto drive off all free peroxide, but low enough not to destroy thechlorine dioxide. McNicholas et al. States that temperatures “muchbelow” 70 degrees C. are ineffective to drive of the free peroxide inthe solution and that temperatures should not exceed 92 degrees C.because at higher temperatures the chlorine dioxide will be driven off.McNicholas further states that, although not “entirely understood,” itwas believed that heating of the solution to drive off free peroxide wasnecessary because any free hydrogen peroxide allowed to remain in thesolution would act as a leaching agent to release the chlorine dioxidefrom the solution.

ii. Antibiotic Preparations

Antibiotic compounds have also been commonly used for the therapeutictreatment of bums, wounds and skin infections. While antibiotics mayprovide an effective form of treatment, several dangers are oftenassociated with the use of antibiotics in the clinical environment.These dangers may include but are not limited to: (1) changes in thenormal flora of the body, with resulting “superinfection” due toovergrowth of antibiotic resistant organisms; (2) direct antibiotictoxicity, particularly with prolonged use which can result in damage tokidneys, liver and neural tissue depending upon the type of antibiotic;(3) development of antibiotic resistant microbial populations which defyfurther treatment by antibiotics.

B. Difficult-To-Treat Dermal Disorders Other Than Wounds, Burns,Abrasions and Infections

While even minor wounds and abscesses can be difficult to treat incertain patients and/or under certain conditions, there are well knowndermal disorders such as psoriasis and dermal ulcerations, which presentparticular challenges for successful treatment.

i. Psoriasis

Psoriasis is a noncontagious skin disorder that most commonly appears asinflamed swollen skin lesions covered with silvery white scale. Thismost common type of psoriasis is called “plaque psoriasis”. Psoriasiscomes in many different variations and degrees of severity. Differenttypes of psoriasis display characteristics such as pus-like blisters(pustular psoriasis), severe sloughing of the skin (erythrodermicpsoriasis), drop-like dots (guttate psoriasis) and smooth inflamedlesions (inverse psoriasis).

The cause of psoriasis is not presently known, though it is generallyaccepted that it has a genetic component, and it has recently beenestablished that it is an autoimmune skin disorder. Approximately one inthree people report a family history of psoriasis, but there is nopattern of inheritance. There are many cases in which children with noapparent family history of the disease will develop psoriasis.

The occurrence of psoriasis in any individual may depend on someprecipitating event or “trigger factor.” Examples of “trigger factors”believed to affect the occurrence of psoriasis include systemicinfections such as strep throat, injury to the skin (the Koebnerphenomenon), vaccinations, certain medications, and intramuscularinjections or oral steroid medications. Once something triggers aperson's genetic tendency to develop psoriasis, it is thought that inturn, the immune system triggers the excessive skin cell reproduction.

Skin cells are programmed to follow two possible programs: normal growthor wound healing. In a normal growth pattern, skin cells are created inthe basal cell layer, and then move up through the epidermis to thestratum corneum, the outermost layer of the skin. Dead cells are shedfrom the skin at about the same rate as new cells are produced,maintaining a balance. This normal process takes about 28 days from cellbirth to death. When skin is wounded, a wound healing program istriggered, also known as regenerative maturation. Cells are produced ata much faster rate, theoretically to replace and repair the wound. Thereis also an increased blood supply and localized inflammation. In manyways, psoriatic skin is similar to skin healing from a wound or reactingto a stimulus such as infection.

Lesional psoriasis is characterized by cell growth in the alternategrowth program. Although there is no wound at a psoriatic lesion, skincells (called “keratinocytes”) behave as if there is. Thesekeratinocytes switch from the normal growth program to regenerativematuration. Cells are created and pushed to the surface in as little as2-4 days, and the skin cannot shed the cells fast enough. The excessiveskin cells build up and form elevated, scaly lesions. The white scale(called “plaque”) that usually covers the lesion is composed of deadskin cells, and the redness of the lesion is caused by increased bloodsupply to the area of rapidly dividing skin cells.

Although there is no known cure for psoriasis, various treatments havebeen demonstrated to provide temporary relief in some patients. However,the effectiveness of the currently accepted treatments for psoriasis issubject to considerable individual variation. As a result, patients andtheir physicians may have to experiment and/or combine therapies inorder to discover the regimen that is most effective. The currentlyavailable treatments for psoriasis are often administered in step-wisefashion. Step 1 treatments include a) topical medications (e.g., topicalsteroids, topical retinoids), b) systemic steroids, c) coal tar, d)anthralin, e) vitamin D3; and sunshine. Step 2 treatments include a)phototherapy (e.g, ultraviolet radiation), b) phochemotherapy (e.g., acombination of a topically applied radiation-activated agent followed byradiation to activate the agent) and c) combination therapy. Step 3treatments include a) systemic drug therapies such as methotrexate, oralretinoids and cyclosporine and b) rotational therapy.

ii. Dermal Ulcerations

Dermal ulcerations are known to occur as a result of pressure, wear, orprimary/secondary vascular disorders. Dermal ulcerations are generallyclassified according to their etiology, as follows:

a. Decubitus/Pressure Ulcers—A decubitus ulcer or pressure sore is alesion caused by unrelieved pressure resulting in damage of theunderlying tissue. Decubitus ulcers usually develop over a bonyprominence such as the elbow or hip. The unrelieved pressure, along withnumerous contributing factors, leads to the skin breakdown andpersistent ulcerations.

b. Venous Ulcers—Venous ulcers may result from trauma or develop afterchronic venous insufficiency (CVI). In CVI, venous valves don't closecompletely, allowing blood to flow back from the deep venous systemthrough the perforator veins into the superficialvenous system. Overtime, the weight of this column of blood causes fluid and protein toexude into surrounding tissues, resulting in swollen, hyperpigmentedankles, tissue breakdown, and ulceration. Venous ulcers may be shallowor extend deep into muscle.

c. Arterial Ulcers—Leg ulcers also can develop in patients with arterialinsufficiency caused by arterial vessel compression or obstruction,vessel wall changes, or chronic vasoconstriction. Smokers face anespecially high risk of arterial disease because nicotine constrictsarteries, encourages deposits of atherosclerotic plaque, and exacerbatesinflammatory arterial disease (Buerger's disease) and vasoconstrictivedisease (Raynaud's disease or phenomenon). Arterial ulcers, caused bytrauma to an ischemic limb, can be very painful,

d. Diabetic Ulcers—Arterial insufficiency can be the cause of anonhealing ulcer in a patient with diabetes. However, most diabeticulcers result from diabetic neuropathy—because the patient can't feelpain in his foot, he's unaware of injuries, pressure from too-tightshoes, or repetitive stress that can lead to skin breakdown.

There remains a need in the art for the formulation and development ofnew disinfectants and topically applicable preparations for thetreatment of dermal disorders, such as wounds, burns, abrasions,infections, ulcerations, psoriasis and acne.

SUMMARY OF THE INVENTION

The present invention provides antimicrobial preparations (e.g.,solutions, gels, ointments, creams, etc.) for disinfection of articlesor surfaces (e.g., contact lenses, counter tops, etc.), antisepsis ofskin or other body parts, prevention or minimization of scarring, and/ortreatment or prophylaxis of dermal (Le., skin or mucous membrane)disorders (e.g., wounds, burns, infections, cold sores, ulcerations,psoriasis, scar forming lesions, acne). The antimicrobial preparationsof this invention generally comprise from about 0.001% to about 0.10 byweight of a metal chlorite in combination with from 0.001% to 0.05% of aperoxy compound such as hydrogen peroxide. Additionally, thechlorite/peroxide preparations of the present invention may containadditional components such as polymeric lubricants and surfactants,and/or may be formulated in a polymeric drug delivery system orliposomal preparation. The chlorite/peroxide preparations of the presentinvention have broad antimicrobial activity, including for exampleactivity against gram negative and gram positive bacteria, yeasts andfungi. Moreover, when applied or administered to treat dermal disorders(e.g.,wounds, bums, infections, ulcerations, acne and psoriasis), thechlorite/peroxide preparations of the present invention will not onlyprevent or lessen microbial infection, but will additionally provideoxygen to the affected tissue, aid in healing and deter scar formation.

Further in accordance with the invention, there are provided methods fordisinfection of items (e.g., contact lenses) and methods for treatmentof dermal disorders (e.g.,wounds, bums, infections, ulcerations andpsoriasis) by application or administration of a chlorite/peroxidepreparation of the present invention. Further in accordance with theinvention, there are provided methods for deterring scar formation byapplication or administration of a chlorite/peroxide preparation of thepresent invention.

Further aspects and objects of the present invention will becomeapparent to those of skill in the art upon reading and understanding ofthe following detailed description and the examples set forth therein.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The following detailed description and examples are provided for thepurpose of describing certain exemplary embodiments of the inventiononly, and are not intended to limit the scope of the invention in anyway.

The present invention provides preparations which contain chlorite(e.g., a metal chlorite) in combination with a small amount of hydrogenperoxide in neutral aqueous (pH 6.8-7.8, preferably pH 7.0-7.4)solution. These preparations exhibit synergistic antimicrobial activitywithout generating chlorine dioxide during storage, thereby renderingthe stability of these solutions acceptable for pharmaceutical use. Forexample, an aqueous solution containing 400 ppm chlorite plus 100 ppmhydrogen peroxide remains stable beyond 18 months at room temperature,and is effective to reduce candida albicans activity by 1.0 log within a6 hrs of challenge, even though the individual components of suchsolution are ineffective when applied separately at the sameconcentrations, to reduce candida albicans activity. Additionally, thehydrogen peroxide present within the chlorite/peroxide solutions of thepresent invention readily decomposes into molecular oxygen and water,upon contact with the peroxidase and catalase enzymes present in tissueand/or some body fluids. Such in situ generation of molecular oxygencontributes to cell vitality and enhances wound healing.

The chlorite/H₂O₂ solutions of the present invention are sufficientlystable to be formulated in combination with polymeric lubricants(non-ionic and/or anionic; e.g., HPMC, Methocel, CMC, etc.) and/or incombination with block polymer based surfactants (e.g., pluronics). Forexample, an aqueous chlorite/hydrogen peroxide system can be formulatedtogether with methocel as a lubricant and pluronics as a surfactant forcontact lens disinfectant solution (viscosity up to 50 cps at 25 degreesC.) in an ophthalmically acceptable tonicity (e.g., osmolality of atleast about 200 mOsmol/kg) and a buffer to maintain the pH of theformulation within an acceptable physiological range. The formulation ofthe contact lens disinfection solution contains chlorite preferably fromabout 0.03 to about 0.06 weight/volume percent and hydrogen peroxidepreferably from about 0.0002 to about 0.05 weight/volume percent. Again,the presence of hydrogen peroxide provides the beneficial oxygenmolecule to the cornea upon contact with catalase in the tear.

A. Formulations

The chlorite/peroxide preparations of the present invention may beformulated in various ways, including liquid solutions, gels, ointments,creams, sprays, etc. Set forth herebelow are but a few examples of thetypes of specific formulations which may be prepared in accordance withthis invention.

A Stable Chlorite/Peroxide Liquid Solution

The following Formula 1 is a presently preferred formulation of a liquidchlorite/peroxide solution of the present invention:

FORMULA 1 Sodium Chlorite  0.02%-0.10% Hydrogen Peroxide 0.005%-0.01%Methocel A 0.05%-0.2% Boric Acid 0.15% Sodium Chloride 0.75% PluronicF-68  0.1% HCl or NaOH Adjust pH 7.4 Purified water Q.S. to volume

The chlorite/peroxide solutions of the present invention, such as thesolution of the above-shown preferred formulation, may be used for avariety of medical and non-medical applications including but notnecessarily limited to a) disinfection of articles and surfaces such ascontact lenses, medical/dental instruments, counter tops, treatmenttables, combs and brushes, etc; antisepsis of skin or body parts (e.g.,a disinfectant hand wash, antiseptic facial scub, etc.) and b) treatmentor prophylaxix of dermal (I.e., skin or mucous membrane) disorders suchas wounds, bums, infections, ulcerations, cold sores, psoriasis, acne,and c) deterrence or prevention of scar formation.

As pointed out earlier, the chlorite/hydrogen peroxide system of thepresent invention is sufficiently stable to be formulated in a polymericgel form or in a paste form, Furthermore, such polymeric gel or pasteformulation can contain polymers which delay or control the release ofthe chlorite/hydrogen peroxide (e.g,, a sustained release deliverysystem). Such sustained release formulations provide outstandingbenefits of increasing therapeutic index by maintaining the effectiveconcentration of chlorite/H202 for a prolonged time on the injuredsites, by preventing the injured sites from external microbialcontamination by forming a seal over the injured sites, and by providingoxygen molecule to the injured tissues. Unlike the conventionalointment, the polymeric gel provides a dry, clean, and comfortablecoating on the injured sites upon application. Such gel formulations maycontain polymeric drug delivery vehicles like hydroxypropylmethylcellulose (HPMC), methylcellulose (Methocel),hydroxyethylcellulose (HEC), and carboxymethylcellulose (CMC), etc.

ii. A Stable Chlorite/Peroxide Gel

The following Formula 2 is a presently preferred formulation of achlorite/peroxide gel of the present invention:

FORMULA 2 Sodium Chlorite  0.02%-0.10% Hydrogen Peroxide 0.005%-0.01%Methocel A  2.0% Boric Acid 0.15% Sodium Chloride 0.75% Pluronic F-68 0.1% HCl or NaOH Adjust pH 7.4 Purified water Q.S. to volume

Any of the preparations of the present invention may be formulated forsustained release of the active components by forming liposomes of thepreparing in accordance with well known liposomal forming techniquesand/or by adding to the formulation a pharmaceutically acceptable andeffective amount (e.g., typically 1-20 percent by weight) of a sustainedrelease component such as a polymer matrix or one or more of thefollowing:

-   -   a cellulose ester;    -   hydroxymethylpropyl cellulose;    -   methylhydroxyethyl cellulose;    -   hydroxypropyl cellulose;    -   hydroxyethyl cellulose;    -   carboxymethyl cellulose;    -   a salt of a cellulose ester;    -   cellulose acetate;    -   hydroxypropylmethyl cellulose phthalte;    -   methacrylic acid-methyl methacrylate copoymer;    -   methacrylic acid-ethyl acetate copolymer;    -   polyvinylpyrrolidone;    -   polyvinyl alcohol;    -   a phospholipid;    -   cholesterol;    -   a phospholipid having a neutral charge;    -   a phospholipid having a negative charge;    -   dipalmytoyl phoshatidyl choline;    -   dipalmytoyl phoshatidyl serine; and,    -   sodium salts thereof.

B. Examples of Therapeutic Applications

The following are specific examples of therapeutic applications of thechlorite/peroxide preparations of the present invention.

i. EXAMPLE 1 Treatment of Psoriasis-No Crossover

A human patient having psoriasis plaques present on both arms is treatedas follows:

-   -   Twice daily application to plaques on the left arm only, of a        chlorite/peroxide solution having the following formulation:

Sodium Chlorite 0.06% Hydrogen Peroxide 0.01% HPMC  2.0% Boric Acid0.15% HCl or NaOH to adjust pH 7.4 Purified water Q.S. to volume

-   -   Twice daily application to plaques on the right arm only of a        commercially available 0.1% triamcinolone acetonide cream.

The chlorite/peroxide treated psoriatic plaques on the right arm beganto become less severe within 24 hours of beginning treatment and hadsubstantially disappeared within 3 days of beginning treatment. However,the triamcinolone acetonide treated psoriatic plaques present on theleft arm remained unchanged and inflamed during the two (2) weektreatment period.

ii. EXAMPLE 2 Treatment of Psoriasis-Crossover

A human patient having psoriasis plaques present on both arms is treatedfor two (2) weeks, as follows:

-   -   Twice daily application to plaques on the left arm only, of a        chlorite/peroxide solution having the following formulation:

Sodium Chlorite 0.06% Hydrogen Peroxide 0.01% HPMC  2.0% Boric Acid0.15% HCl or NaOH to adjust pH 7.4 Purified water Q.S. to volume/100%

-   -   Twice daily application to plaques on the right arm only of a        commercially available 0.1% triamcinolone acetonide cream.

The chlorite/peroxide treated psoriatic plaques on the right arm beganto become less severe within 24 hours of beginning treatment and hadsubstantially disappeared within 1 week of beginning treatment. However,the triamcinolone acetonide treated psoriatic plaques present on theleft arm remained unchanged and inflamed during the two (2) weektreatment period.

Beginning the day after the end of the initial two (2) week treatmentperiod, and continuing for a second two (2) week treatment period, thepatient was treated as follows:

-   -   Twice daily application to plaques on the left arm only of the        same commercially available 0.1% triamcinolone acetonide cream        described herebove in this example.    -   Twice daily application to plaques on the right arm only, of the        same chlorite/peroxide sustained release gel described hereabove        in this example.

Within 24 hours of commencing the second treatment period, the psoriaticlesions on the right arm began to subside. By day 3 and continuingthrough the end of the second two (2) week treatment period, thepsoriatic lesions on the right arm had substantially disappeared.

iii. EXAMPLE 3 Treatment of Cold Sores

A patient with painful, fluid-containing cold sores (i.e., chancresores) on his lips was treated twice daily by application to the lips ofa chlorite/peroxide preparation prepared in accordance with Formula 1above.

Within 6 to 12 hours of the first application of the chlorite/peroxidepreparation, the patient reported that the pain had subsided. Within 24hours of the first application of the chlorite/peroxide preparation, thefluid contained within the cold sores had substantially dissipated andthe cold sores appeared dry. Within 6 days of the first application ofthe chlorite/peroxide preparation the cold sores had substantiallydisappeared and the lips appeared normal, whereas cold sores of suchseverity typically require substantially longer than 6 days tocompletely disappear and heal.

iv. EXAMPLE 4 Treatment of Venous Ulcer

A patient with a venous ulcer on the right leg of 3-4 cm diameter whichhad been present for 9-12 months was treated by twice daily applicationto the ulcer of gauze soaked with a chlorite/peroxide liquid solutionprepared in accordance with Formula 1 above.

Within 3 days after commencement of treatment the ulcer appeared cleanand dry. Within 14 days of the commencement of treatment the ulcer beganto decrease in size and healthy new tissue was observed about itsperiphery. At 35 days after commencement of treatment, the ulcer hadcompletely healed, without scarring, and the area where the ulcer hadbeen located was free of pain.

v. EXAMPLE 5 Treatment of Diabetic Decubitus Ulcer

A non-ambulatory, diabetic patient with decubitus ulcers on both legsand some toes, of 12-18 month duration, was treated by daily applicationof clean, sterile gauze to the ulcers and saturation of each gauze, 3times each day, with a liquid chlorite/peroxide solution prepared inaccordance with Formula 1 above. Within 4 to 7 days of commencing thechlorite/hydrogen peroxide treatments the ulcers began to appear lessinflamed, clean and dry. About 7 to 10 days after commencement of thechlorite/hydrogen peroxide treatment, granulation tissue began to formwithin the ulcers. Within 12 to 14 days, re-epithelialization wasobserved to have begun within the ulcerated areas except for one toeulcer which had been particularly sever and had permeated to the bone ofthe toe. Within 30 to 45 days of the commencement of treatment, all ofthe ulcers except for the severe toe ulcer had completely closed andre-epithelialized, without irregular scar formation. Also, at 30 to 45days after the commencement of treatment, the toe ulcer had also becomesubstantially smaller (but was not completely closed) and the patientwas able to walk. The liquid and or gell formulations of the presentinvention, such as Formulas 1 and 2 above, may also be applied topicallyto prevent scar formation due to wounds, burns, acne, infections,trauma, surgical incision, or any other scar-forming lesion or disorder.

It will be appreciated by those skilled in the art, that the inventionhas been described hereabove with reference to certain examples andspecific embodiments. However, these are not the only examples andembodiments in which the invention may be practiced. Indeed, variousmodifications may be made to the above-described examples andembodiments without departing from the intended spirit and scope of thepresent invention, and it is intended that ally such modifications beincluded within the scope of the following claims.

What is claimed is:
 1. A chlorine dioxide-free preparation comprising: approximately 0.02-0.10 percent by weight of a chlorite compound; approximately 0.005-0.01 percent by weight of a peroxy compound; sodium chloride; and water; wherein the preparation has a pH in the range of 6.8 to 7,8; and wherein no chlorine dioxide is generated within the solution when stored at room temperature for up to 18 months .
 2. A preparation according to claim 1 wherein the chlorite is present as a metal chlorite.
 3. A preparation according to claim 2 wherein the metal chlorite is selected from the group of metal chlorites consisting of: sodium chlorite; potassium chlorite; calcium chlorite; and, magnesium chlorite.
 4. A preparation according to claim 1 wherein the peroxy compound is hydrogen peroxide.
 5. A preparation according to claim 1 in liquid form, said preparation comprising: Sodium Chlorite  0.02%-0.10%; Hydrogen Peroxide 0.005%-0.01%; Methocel A 0.05%-0.2%; Boric Acid 0.15%; Sodium Chloride 0.75%; Pluronic F-68  0.1%; HCl or NaOH to adjust pH to about 7.4; and, Purified water Q.S. to volume.


6. A preparation according to claim 1 in gel form, said preparation comprising: Sodium Chlorite  0.02%-0.10% Hydrogen Peroxide 0.005%-0.01% Methocel A 0.05%-2.0% Boric Acid 0.15% Sodium Chloride 0.75% Pluronic F-68  0.1% HCl or NaOH Adjust pH 7.4 Purified water Q.S. to volume


7. A preparation according to claim 1 further comprising: a sustained delivery component which limits the rate at which the chlorite becomes available for generation of chlorine dioxide and hydrogen peroxide becomes available for generation of oxygen.
 8. A sustained release preparation according to claim 7, wherein the sustained delivery component comprises a polymer matrix.
 9. A sustained release preparation according to claim 7, wherein the sustained delivery component comprises a liposome.
 10. A sustained release preparation according to claim 7, wherein the sustained delivery component is selected from the group consisting of: a cellulose ester; hydroxymethylpropyl cellulose; methylhydroxyethyl cellulose; hydroxypropyl cellulose; hydroxyethyl cellulose; carboxymethyl cellulose; a salt of a cellulose ester; cellulose acetate; hydroxypropylmethyl cellulose phthalte; methacrylic acid-methyl methacrylate copoymer; methacrylic acid-ethyl acetate copolymer; polyvinylpyrrolidone; polyvinyl alcohol; a phospholipid; cholesterol; a phospholipid having a neutral charge; a phospholipid having a negative charge; dipalmytoyl phoshatidyl choline: dipalmytoyl phoshatidyl serine; and, sodium salts thereof.
 11. A sustained release preparation according to claim 7, wherein the sustained delivery component comprises 1-20 percent by weight of the preparation.
 12. A preparation according to claim 1 which is a liquid,
 13. A preparation according to claim 1 which is a gel.
 14. A preparation according to claim 1 which is a cream.
 15. A preparation according to claim 1 which is an ointment.
 16. A preparation according to claim 1 which is a contact lens solution, wherein said preparation further comprises at least one additional component selected from: polymeric lubricants, non-ionic polymeric lubricants, anionic polymeric lubricants; HPMC, Methocel and carboxymethylcellulose.
 17. A preparation according to claim 16 wherein the surfactant comprises a block polymer based surfactant. 